Exposure of Mice during Spermatogenesis: A Role of Inhibitor Kinase 2 in Pro-Opiomelanocortin Neurons
JournalEnvironmental Health Perspectives
PublisherResearch Triangle Park, N. C. National Institute of Environmental Health Sciences
MetadataShow full item record
AbstractEpidemiological studies have shown that exposure to ambient fine particulate matter with aerodynamic diameter less than or equal to 2.5 μm (PM2.5) correlates with a decrease in sperm count, but the biological mechanism remains elusive. Objectives: This study tested whether hypothalamic inflammation, an emerging pathophysiological mediator, mediates the development of lower epididymal sperm count due to PM2.5 exposure. Methods: Inhibitor κB kinase 2 (IKK2) was conditionally knocked out either in all neurons or subtypes of hypothalamic neurons of mice. Effects of concentrated ambient PM2.5 (CAP) exposure on hypothalamic inflammation, the hypothalamic–pituitary–gonadal (HPG) axis, and epididymal sperm count of these mouse models were then assessed. Furthermore, to test whether hypothalamic inflammation is sufficient to decrease sperm production, we overexpressed constitutively active IKK2 (IKK2ca) either in all neurons or subtypes of hypothalamic neurons and assessed hypothalamic inflammation, the HPG axis, and sperm production of these overexpression mouse models. Results: CAP-exposed wild-type control mice vs. filtered air (FA)-exposed wild-type control mice had a higher expression of hypothalamic inflammatory markers, lower functional indexes of the HPG axis, and a lower epididymal sperm count. In contrast, all these measurements for CAP- vs. FA-exposed mice deficient of IKK2 in all neurons were comparable. We also found that overexpression of IKK2ca in either all neurons or pro-opiomelanocortin (POMC) neurons only, but not in Agouti-related protein (AgRP) neurons only, resulted in lower functional indexes of the HPG axis and a lower epididymal sperm count. Moreover, we showed that CAP- vs. FA-exposed mice deficient of IKK2 in POMC neurons had a comparable expression of hypothalamic inflammatory markers, comparable functional indexes of the HPG axis, and a comparable epididymal sperm count. Discussion: This mouse model study shows a causal role of IKK2 of POMC neurons in the development of lower epididymal sperm count due to PM2.5 exposure, providing a mechanistic insight into this emerging pathogenesis.
Keywordinhibitor kB kinase 2 (IKK2)
Particulate Matter--adverse effects
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16587
- Concentrated Ambient PM<sub>2.5</sub>-Induced Inflammation and Endothelial Dysfunction in a Murine Model of Neural IKK2 Deficiency.
- Authors: Chen M, Qin X, Qiu L, Chen S, Zhou H, Xu Y, Hu Z, Zhang Y, Cao Q, Ying Z
- Issue date: 2018 Feb 5
- Exposure to Concentrated Ambient PM2.5 Compromises Spermatogenesis in a Mouse Model: Role of Suppression of Hypothalamus-Pituitary-Gonads Axis.
- Authors: Qiu L, Chen M, Wang X, Qin X, Chen S, Qian Y, Liu Z, Cao Q, Ying Z
- Issue date: 2018 Mar 1
- From the Cover: Lung-Specific Overexpression of Constitutively Active IKK2 Induces Pulmonary and Systemic Inflammations but Not Hypothalamic Inflammation and Glucose Intolerance.
- Authors: Chen M, Zhou H, Xu Y, Qiu L, Hu Z, Qin X, Chen S, Zhang Y, Cao Q, Abu-Amer Y, Ying Z
- Issue date: 2017 Nov 1
- Concentrated ambient PM<sub>2.5</sub> exposure affects mice sperm quality and testosterone biosynthesis.
- Authors: Yang Y, Yang T, Liu S, Cao Z, Zhao Y, Su X, Liao Z, Teng X, Hua J
- Issue date: 2019
- Central IKK2 Inhibition Ameliorates Air Pollution-Mediated Hepatic Glucose and Lipid Metabolism Dysfunction in Mice With Type II Diabetes.
- Authors: Sun Q, Zhang G, Chen R, Li R, Wang H, Jiang A, Li Z, Kong L, Fonken LK, Rajagopalan S, Sun Q, Liu C
- Issue date: 2018 Jul 1